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Molecular and Cellular Biochemistry

, Volume 455, Issue 1–2, pp 119–125 | Cite as

Analgesic-antitumor peptide inhibits angiogenesis by suppressing AKT activation in hepatocellular carcinoma

  • Qingxin Cao
  • Wuguang Lu
  • Tingting Zhou
  • Yu Liu
  • Xueting Cai
  • Jin ZhuEmail author
  • Peng CaoEmail author
Article
  • 170 Downloads

Abstract

Hepatocellular carcinoma (HCC) is one of leading causes of cancer-related death, and its increasing incidence worldwide is a cause for concern. The recombinant analgesic-antitumor peptide (rAGAP), a protein consisting of small ubiquitin-related modifier linked with a hexa-histidine tag, exhibited the antitumor activity in HepG2 tumors in our previous study. However, the underlying molecular mechanism of its antitumor activity was still elusive. In this work, we found that treatment with rAGAP reduced phosphorylation of AKT at non-toxic doses in HepG2 cells in vitro. More importantly, treatment of HepG2 cells with rAGAP downregulated protein expression of HIF-1α, suppressed activities of HIF, reduced secretion of VEGF and IL-8, and suppressed HepG2-induced tube formation by HUVEC, which was reversed by co-incubation with SC-79 (an AKT activator). Furthermore, in tumors of athymic mice with HepG2, treatment with rAGAP reduced phosphorylation of AKT, downregulated protein expression of HIF-1α and VEGF, and microvessel density marked by positive CD31 staining. Collectively, rAGAP inhibited angiogenesis by suppressing AKT activation, which partly explained its antitumor activity in HCC.

Keywords

Recombinant analgesic-antitumor peptide HepG2 Angiogenesis AKT Hepatocellular carcinoma 

Abbreviations

HCC

Hepatocellular carcinoma

HIF-1α

Hypoxia-inducible factor 1 alpha

HUVEC

Human umbilical vein endothelial cells

IL-8

Interleukin 8

rAGAP

Recombinant antitumor-analgesic peptide

VEGF

Vascular endothelial growth factor

Notes

Author contributions

Conception and design of the experiments: QC, WL, JZ, PC. Collection, analysis, and interpretation of data: QC, WL, TZ, YL, XC, JZ, PC. Drafting the article: QC, WL, JZ, PC.

Funding

This study was supported by the project of Quality guarantee system of Chinese Herbal Medicines (201507002), the National Natural Science Foundation of China (81622048, 81473377), China Postdoctoral Science Foundation (2016M601609), and Science Foundation for Distinguished Young Scholars of Jiangsu Province (BK20140049).

Compliance with ethical standards

Conflict of interest

We declare that we have no conflict of interest.

Supplementary material

11010_2018_3475_MOESM1_ESM.docx (494 kb)
Supplementary material 1 (DOCX 493 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Huadong Medical Institute of BiotechniquesNanjingPeople’s Republic of China
  2. 2.Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingPeople’s Republic of China
  3. 3.Laboratory of Cellular and Molecular BiologyJiangsu Province Academy of Traditional Chinese MedicineNanjingPeople’s Republic of China
  4. 4.Drum Tower HospitalNanjingPeople’s Republic of China

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